Share This

Promising results of the Phase I clinical trial of the generic drug BCG (bacillus Calmette-Guerin) to treat advanced type I diabetes were announced June 26 at the American Diabetes Association scientific sessions in San Diego. A research team led by Denise Faustman, MD, PhD, director of the Massachusetts General Hospital (MGH) Immunobiology Laboratory is presenting two abstracts (No. 2240-PO and No. 0057-LB) -- the first which describes the apparent reproduction in human patients of the mechanism that reversed type 1 diabetes in a mouse model and the second proposing that lack of a key part of that mechanism may explain why recent trials of an antibody-based diabetes therapy were not successful. The Iacocca Foundation has been the primary supporter of this work.

Related Articles

"We found that even low doses of BCG could transiently reverse type 1 diabetes in human patients," Faustman says. "One of the key components of this study was our development of a way to measure the death of the autoreactive T cells that destroy the ability of the pancreas to produce insulin. Not only did we observe and measure the death of these self-targeting immune cells, but we also saw evidence of restoration of insulin production even in patients who've had type 1 diabetes for more than a decade."

A generic drug with 90 years of safety data, BCG is currently approved by the U.S. FDA for vaccination against tuberculosis and for the treatment of bladder cancer. BCG is known to elevate levels of the immune modulator tumor necrosis factor (TNF), which previous work in Faustman's lab showed can temporarily eliminate the abnormal white blood cells responsible for type 1 diabetes in both humans and mice. The Phase I double-blinded clinical trial enrolled six long-term type 1 diabetes patients, diagnosed for an average of 15 years. The participants were randomly assigned to receive two injections of either BCG or a placebo spaced four weeks apart.

Blood samples from the participants with diabetes were also compared with samples from six nondiabetic participants and with reference samples from 75 additional individuals with diabetes and 15 without. Four measurements were analyzed for each sample -- levels of autoreactive T cells; levels of the regulatory T cells that help control the immune response; levels of GAD autoantibodies, which are a marker of pancreas activity; and levels of C-peptide, a marker of insulin secretion.

Most participants treated with BCG showed increases in both the death of autoreactive T cells and in levels of the protective regulatory T cells. A temporary but statistically significant elevation in C-peptide levels, suggesting a restoration of insulin production, was also observed in the BCG-treated patients. Unexpectedly, the same responses were seen in one of the placebo-treated patients who, after enrolling in the study, coincidently developed infection with the Epstein-Barr virus, which is known to induce expression of TNF.

"These data support our hypothesis that BCG may benefit human type 1 diabetes by boosting TNF levels," says Faustman. "The data from the EBV-infected patient show that induction of TNF expression from diverse sources may have been a missing component in two recent, unsuccessful Phase III trials that tested antibodies against the immune molecule CD3 in type 1 diabetes patients. Those trials were specifically designed to avoid reactivating any latent EBV infection, but blocking EBV activation could also block TNF expression."

In addition to providing major funding for the now-completed Phase I trial, the Iacocca Foundation has committed to a leadership role in the Phase II clinical trial that was initiated at MGH earlier this month. Currently $8.5 million has been raised out of a total of $25 million needed to conduct the Phase II study over the next three years.

Featured Research

Mar. 31, 2015  Researchers have illuminated an important distinction between mice and humans: how human livers heal. The difference centers on a protein called PPAR alpha which activates liver ... full story

Mar. 31, 2015  Researchers have recorded the first direct observations of the micro-scale mechanisms behind the ability of skin to resist tearing. The results could be applied to the improvement of artificial skin, ... full story

Mar. 31, 2015  Fewer than half of the physicians trained in the United States in 2013 received formal education or training on the subject of exercise, according to new research. "There are immense medical benefits ... full story

Mar. 31, 2015  Memory and as well as connections between brain cells were restored in mice with a model of Alzheimer's given an experimental cancer drug, researchers report. "With this treatment, cells under ... full story

Mar. 31, 2015  Increasing state alcohol taxes could prevent thousands of deaths a year from car crashes, say researchers, who found alcohol-related motor vehicle crashes decreased after taxes on beer, wine and ... full story

Mar. 31, 2015  Alcoholism takes a toll on every aspect of a person's life, including skin problems. Now, a new research report helps explain why this happens and what might be done to address it. "The clinical ... full story

Mar. 31, 2015  A new population of 'memory' immune cells has been discovered by scientists, throwing light on what the body does when it sees a microbe for the second time. This insight, and others like it, will ... full story

Mar. 31, 2015  Coronary heart disease and stroke, two of the leading causes of death in the United States, are diseases associated with heightened platelet reactivity. A new study in humans suggests an underlying ... full story

Mar. 31, 2015  A new study had researchers seeking answers to why the therapeutic benefit afforded by SSRIs was so limited in children and teenagers. If researchers can uncover the biological mechanisms preventing ... full story

Featured Videos

Solitair Device Aims to Takes Guesswork out of Sun Safety

Reuters - Innovations Video Online (Mar. 31, 2015)  The Solitair device aims to take the confusion out of how much sunlight we should expose our skin to. Small enough to be worn as a tie or hair clip, it monitors the user&apos;s sun exposure by taking into account their skin pigment, location and schedule. Matthew Stock reports.
Video provided by Reuters

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015)  Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline.
Video provided by Washington Post

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015)  Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17
Video provided by AFP

Related Stories

Aug. 19, 2014  A variant of the century-old vaccine Bacille Calmette-Guerin is superior to BCG in protecting against tuberculosis in animal models, and also cross protects against leprosy, researchers report. ... full story

Oct. 1, 2013  A new vaccine has been developed to act as a booster to Bacille Calmette Guerin (BCG), currently the only TB vaccine available. BCG was developed in the 1920s and has been used worldwide. The new ... full story

Aug. 9, 2012  A phase I clinical trial has confirmed that use of a generic vaccine to raise levels of an immune system modulator can cause the death of autoimmune cells targeting the insulin-secreting cells of the ... full story

May 24, 2011  Clinical trials for a new bladder cancer therapy show promising interim results. Lead researcher Alvaro Morales says that the breakthrough using the drug Urocidin follows thirty years of his research ... full story

June 28, 2010  Researchers in Massachusetts have announced the completion of the Phase I BCG clinical trial in type 1 diabetes. Plans for the Phase II clinical study, which will continue the investigation of ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.